Lipid packing in biological membranes governs protein localization and membrane permeability

Tripathy, M and Srivastava, A (2023) Lipid packing in biological membranes governs protein localization and membrane permeability. In: Biophysical Journal, 122 (13). pp. 2727-2743.

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Abstract

Plasma membrane (PM) heterogeneity has long been implicated in various cellular functions. However, mechanistic principles governing functional regulations of lipid environment are not well understood due to the inherent complexities associated with the relevant length and timescales that limit both direct experimental measurements and their interpretation. In this context, computer simulations hold immense potential to investigate molecular-level interactions and mechanisms that lead to PM heterogeneity and its functions. Herein, we investigate spatial and dynamic heterogeneity in model membranes with coexisting liquid ordered and liquid disordered phases and characterize the membrane order in terms of the local topological changes in lipid environment using the nonaffine deformation framework. Furthermore, we probe the packing defects in these membranes, which can be considered as the conjugate of membrane order assessed in terms of the nonaffine parameter. In doing so, we formalize the connection between membrane packing and local membrane order and use that to explore the mechanistic principles behind their functions. Our observations suggest that heterogeneity in mixed phase membranes is a consequence of local lipid topology and its temporal evolution, which give rise to disparate lipid packing in ordered and disordered domains. This in turn governs the distinct nature of packing defects in these domains that can play a crucial role in preferential localization of proteins in mixed phase membranes. Furthermore, we observe that lipid packing also leads to contrasting distribution of free volume in the membrane core region in ordered and disordered membranes, which can lead to distinctive membrane permeability of small molecules. Our results, thus, indicate that heterogeneity in mixed phase membranes closely governs the membrane functions that may emerge from packing-related basic design principles.

Item Type:	Journal Article
Publication:	Biophysical Journal
Publisher:	Biophysical Society
Additional Information:	The copyright for this article belongs to the Biophysical Society.
Keywords:	cell membrane; computer simulation; lipid bilayer; membrane; membrane microdomain; metabolism; permeability
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	25 Jul 2023 07:00
Last Modified:	25 Jul 2023 07:00
URI:	https://eprints.iisc.ac.in/id/eprint/82642

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